Prostate cancer is the most frequent cause of cancer in men, yet few risk factors for this disease have been identified. Some prior studies suggest that sexual behavior and associated exposure to sexually transmitted agents enhance risk In particular, number of sexual partners, age at first intercourse, sexual frequency, history of gonorrhea and syphilis, and serologic evidence of syphilis and oncogenic subtypes of human papillomavirus (HPV) have been associated with risk of prostate cancer, but results have not been confirmed. In a recent study of risk factors for prostate cancer in men under age 65 years, we found a significant increase in risk with increasing number of female sexual partners (trend p <0.001), which we hypothesize is related to prior exposure to I-IPV-16 or -18. To test this hypothesis, we propose a population-based case-control study that will analyze stored serum from histologically confirmed prostate cancer cases (n=648) diagnosed during 1993-1996 and ascertained by the Seattle-Puget Sound SEER registry and from control men (n--571) without a history of prostate cancer and frequency matched on age to cancer cases. Virus-like particle ELISA serologic assays will be used to detect BPV-16 and -18. Detailed data on known and suspected risk factors for prostate cancer will be available from in-person interviews. Unconditional logistic regression will be used to estimate relative risks associated with HPV- 16/-18 infection, controlling for potential confounding factors. Clinical data on prostate cancer cases will be utilized to assess whether associations with HPV differ according to disease aggressiveness. Results from this study will provide insight on whether or not these oncogenic HPV subtypes play a role in prostate cancer etiology. If there is an association, the results will have important public health implications since both the exposure and the disease are common.